Drosophila as a Model System to Investigate the Effects of Mitochondrial Variation on Innate Immunity

Abstract

Salminen and Vale Mitochondrial Variation in Innate Immunity BOX 1 | Drosophila innate immunity in a nutshell. Drosophila has been extensively utilized as a model system for innate immunity and it has led to many breakthrough in immunity field (6, 114, 115). Drosophila does not possess acquired/adaptive immunity and it relies on humoral and cell-mediated innate immunity for its defense against pathogens, such as bacteria, viruses, fungi, and parasites. Immune mechanisms against these invaders include activation of appropriate signal transduction pathways depending on the invading microbe, involving production of antimicrobial peptides (AMPs), phagocytosis of microbes, wound closure, and a melanization cascade involved in the encapsulation of foreign elements. Similar first-line innate immune defense mechanisms can be found from plants to humans. Humoral Innate Immunity: In Drosophila, the humoral innate immune response to bacterial pathogens is characterized by the production and release of a cocktail of AMPs into the hemolymph. This response is driven by two evolutionarily conserved and largely independent pathways, Immune deficiency (IMD) and Toll pathways (116). The Toll pathway is induced by bacteria containing LYS-type peptidoglycan in their cell walls (mainly Gram-positive bacteria), while the IMD pathway is induced by DAP-type peptidoglycan (mainly Gram-negative) bacteria. These pathways culminate in the translocation of NF-κB dimers to the nucleus leading to infection-specific upregulation of AMPs targeted to clear the infection (117-119). The response to viral pathogens replicating within the host cells involves both the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway (118, 120), RNA interference (RNAi) and antiviral effector molecules (121, 122). Viral infections involve cell-mediated responses like apoptosis and autophagy and humoral responses such as the expression of anti-viral genes, some of which overlap with genes induced upon bacterial and fungal infections, indicating the involvement of the NF-κB signaling upon viral infections. The response to fungal invaders includes both humoral and cellular arms of immunity and involves the expression of AMPs mainly via the Toll pathway. Cell-Mediated Innate Immunity: In Drosophila, the cell-mediated innate immune system consists of hemocytes (blood cells) and is induced by epithelial damage and detection of foreign particles in the hemocoel. Hemocytes function in sealing of epithelial wounds, encapsulating and terminating parasites and engulfing apoptotic corpses [reviewed in (123)]. In Drosophila there are three major lineages of hemocytes: plasmatocytes (phagocytic), crystal cells (melanization) and lamellocytes (encapsulation). Plasmatocytes comprise the majority of the circulating hemocyte population and are responsible for the engulfment of small particles, participate in the encapsulation of foreign material and are able to trigger the systemic humoral immune response to secrete AMPs. Crystal cells usually make up le...

From Flies to Men: ROS and the NADPH Oxidase in Phagocytes

“…On the other hand, the conservation of the signaling components in ROS pathways presents also an opportunity for performing studies in animals of lower complexity. Drosophila might be an excellent model to study the effects of mitochondrial ROS ( Salminen and Vale, 2020 ), considering the availability of suitable genetic tools. The zebrafish, on the other hand, exhibits a CGD-like phenotype upon NOX2 deficiency ( Schoen et al, 2020 ) and offers the possibility to investigate the individual role of ROS in both granulocytes and mononuclear phagocytes.…”

Non-Rodent Genetic Animal Models for Studying Tauopathy: Review of Drosophila, Zebrafish, and C. elegans Models

“…Second, established behavioral assays are relatively simple and limited to directly addressing in-depth cognitive function [140]. Lastly, the lack of some critical organs/tissues homologous to those of vertebrates that may contribute to tauopathy, such as the adaptive immune system, closed blood circulatory system, and blood-brain barrier, might cause inconsistent and unpredictable results when applied to humans [141,142].…”

Midgut Mitochondrial Function as a Gatekeeper for Malaria Parasite Infection and Development in the Mosquito Host

“…Notably, ubiquitous and neuron-specific overexpression of Parkin in adult fruit flies led to a significant increase in fecundity, in addition to lifespan extension (Rana et al, 2013). In a recent review, Salminen and Vale (2020) elegantly argue that variation in mitochondrial function of D. melanogaster, which has many hallmarks of the same biology in mammals, likely drives variation in fruit fly innate immune function. By extrapolation, this variation, which ranges from optimal mitochondrial dynamics to extreme dysfunction, would be predicted to underlie observed tradeoffs between immunity and fecundity observed in fruit flies with abnormal mitochondrial energy metabolism (Buchanan et al, 2018).…”